Ultrasound mediated drug and gene delivery treatment methods using microbubbles are currently being investigated. They have the potential to deliver novel therapeutic agents that have been difficult to deliver in a targeted manner in therapeutically significant doses using conventional techniques. They also offer the potential to treat previously untreatable diseases; reduce side effects, such as toxicity, of current treatments; and reduce dosages of therapeutic agents. One important component of the delivery system is the microbubbles. They enable agent extravasation and transfection when subjected to a suitable ultrasound stimuli. Microbubbles have a limited lifespan when injected in the circulatory system and are typically destroyed shortly after the ultrasound stimulus of sufficient magnitude is applied. Thus, for successful agent delivery, a constant and fresh supply of microbubbles is needed throughout the treatment.
Ultrasound mediated delivery (USMD) of small molecules, genetic material, and other biologicals (from now on referred to collectively as ‘therapeutic agents’ or simply ‘agents’) using ultrasound and microbubbles has been shown in pre-clinical studies to enhance delivery and uptake of these agents. Uptake is by the cell via sonoporation and other mechanisms (most not fully understood).
A number of the advantages of USMD treatments are the same that have enabled current ablative-type ultrasound therapies: the treatments are non-invasive, they have the ability to focus energy deep within the body, they have the ability to precisely target within the tissue region of interest while leaving intervening tissues unaffected, and are of a modality that is non-ionizing, allowing repeated applications without limitations imposed by ultrasound dose.
Thus far, most research in USMD has focused on demonstrating feasibility of the technology (typically by showing enhanced uptake of the agent being delivered) in vitro and in animal models in vivo, and on microbubble and delivery vehicle design activities. Less emphasis has been placed on the design of the ultrasound delivery device itself or the design of treatment plans specifically tailored to USMD treatments. While many current pre-clinical results indicate enhanced agent delivery over a wide range of ultrasound pressures and frequencies, pulse durations, pulse repetition frequencies, and pulsing intervals, USMD devices bring with them their own set of custom requirements that need to be addressed prior to their widespread clinical use.